CN1235571C - Chitosan and fibroin mixed microsphere and its usage and preparing process - Google Patents
Chitosan and fibroin mixed microsphere and its usage and preparing process Download PDFInfo
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- CN1235571C CN1235571C CNB991200276A CN99120027A CN1235571C CN 1235571 C CN1235571 C CN 1235571C CN B991200276 A CNB991200276 A CN B991200276A CN 99120027 A CN99120027 A CN 99120027A CN 1235571 C CN1235571 C CN 1235571C
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Abstract
The present invention discloses a microsphere blended by chitosan and fibroin, purposes thereof, a preparation method thereof and a preparation method with the microsphere being used as a carrier of fenoprofen calcium medicine. Fibroin dissolved in CaCl2-H2O-ethanol solution is blended with chitosan acetic acid solution after dialysis; the blended solution is mixed and stirred with liquid paraffin and dewatered sorbitan laurate; ethyl acetate and glutaraldehyde are added into the blended solution; the product is dried so as to obtain the microsphere blended by chitosan and fibroin. The microsphere can be used as a slow-releasing microsphere carrier for medicine. Fenoprofen calcium dissolved in glacial acetic acid is blended and crosslinked with chitosan solution, fibroin solution and a glutaraldehyde blended crosslinking agent according to the procedures so as to prepare medicine packing microspheres.
Description
The present invention relates to the fall bag medicine method for preparing microsphere of fragrant calcium medicine of the purposes of a kind of chitosan and fibroin mixed microsphere, this mixed microsphere and preparation method and chitosan and the non-promise of fibroin mixed back enclose, belong to chemical field.
Studies show that recently biodegradable polymer is significant to the application of medicine as pharmaceutical carrier, and pharmaceutical pack is wrapped in the polymer microsphere, through active and Passive Control, enter pre-determined target organ or tissue, slowly release, can reduce its toxic and side effects, improve its bioavailability.Chitosan (being called for short CS) is a kind of natural alkaline polysaccharide, and is nonpoisonous and tasteless, has good bioaffinity and biodegradability, and chitosan is unstable under acidic condition, is easy to dissolving.Fibroin (being called for short FB) has another name called fibroin albumen, is the main composition of silkworm silk (accounting for 70%-80%), contain 18 seed amino acids, and fibroin is more acidproof, and strong acid does not have obviously destruction to it.Chitosan and fibroin mixed the two performance of improving.Fenoprofen calcium (Fenoprofen) is the non-steroidal anti-inflammatory analgesic, is used for acute and chronic, rheumatic, rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.Because its biological half-life is shorter, need frequently take medicine, and it is bigger to the intestines and stomach stimulation, therefore makes the untoward reaction that slow releasing preparation can reduce medicining times and medicine.
In recent years, the chitosan that studies show that in a large number both domestic and external can be used as the carrier of medicament slow release preparation, and people such as POLK (J.Pharm.Sci.83,178,1994) report uses chitosan and sodium alginate at CaCl
2Reaction is formed with the microcapsule of polyelectrolyte film in the solution, and in chitosan and the sodium alginate albuminous slow-release microcapsule that has been preparing carriers certain slow releasing function to be arranged.People's such as HARI (J Appl Polym Sci 59,1795,1996) studies show that chitosan and sodium alginate micro gel capsule can be used as the carrier of biomacromolecule albumin and insulin sustained-release oral preparation.People such as THOMAS (JAppl PolymSci 70,2143,1998) report chitosan and sodium alginate reaction are used to prepare the Orally-taken hirudin microcapsule.People such as LIN (Chem Pharm Bull 40,2491,1992) report chitosan and sodium carboxymethyl cellulose form the micropowder grain, can be used as the carrier of the floating microcapsule of theophylline stomach.People such as Wang Yamin (Acta Pharmaceutica Sinica, 31,300,1996) have reported the preparation and the characteristic of cisplatin chitosan microball, the preparation method of people such as Liu Xiangjun (Acta Pharmaceutica Sinica, 26,782,1991) report rotundine/chitosan medicament slow release bead.But the preparation method of chitosan and fibroin mixed microsphere and be used for fall fragrant calcium medicine and make bag medicine microsphere and do not appear in the newspapers of the non-promise of enclose.
Up to the present, the relatively more responsive microsphere of PH still is not reported.Therefore known chitosan and fibroin make mixed microsphere with them all to the PH sensitivity, help being suitable for the sustained release under the different PH conditions, and this mixed microsphere may have the important application prospect in the sustained release medicine.
Based on above situation, the object of the present invention is to provide purposes of a kind of chitosan and fibroin mixed microsphere, this mixed microsphere and preparation method thereof, with this microsphere as enclose the fall preparation method of medicine micro computer ball carriers such as fragrant calcium of non-promise.
For achieving the above object, the technical solution adopted in the present invention is as follows:
A kind of chitosan and fibroin mixed microsphere, it is that fibroin is dissolved in CaCl
2-H
2In the O-alcoholic solution, with the chitosan-acetic acid solution blend, mix stirring after the dialysis, add ethyl acetate, glutaraldehyde blended cross linking products therefrom microsphere with liquid paraffin, anhydrous sorbitol laurate.
Because chitosan and fibroin are all to the PH sensitivity, therefore make the carrier of mixed microsphere useful as drug sustained release with them, behind carrying medicament, can be at the sustained release under the different PH conditions, therefore, this mixed microsphere has the important application prospect in the sustained release medicine.
The preparation method of chitosan and fibroin mixed microsphere:
The NaHCO with 0.5% is removed behind the pupa in the preparation of fibroin solution, Bombyx bombycis
3Solution boils at 100 ℃ that 30min comes unstuck, dry fibroin, and fibroin is dissolved in 1: 8: 2 CaCl of mol ratio
2-H
2In the O-ethanol water, 3 days after-filtration of dialysis get certain density fibroin solution in water then, and this solution is stored in the brown bottle, and is In Shade.
The preparation of chitosan and fibroin mixed microsphere, fibroin solution with 1% and 2% chitosan solution are at normal temperatures in 1: 4 to 4: 1 ratio blend, get above-mentioned blended liquid 10mL and liquid paraffin 10-50mL, anhydrous sorbitol laurate 0.8-1.4g mixes stirring and adds ethyl acetate 2mL after 20～40 minutes, glutaraldehyde 1-2mL stirs and uses acetone thorough washing solid product after 1-2 hour, and 60 ℃ of following vacuum dryings get the chitosan fibroin mixed microsphere.
This microsphere loads medicine can dual mode, and the one, prepare mixed microsphere earlier, adopt the passive load mode to load medicine again, also can in the preparation mixed microsphere, add pharmaceutical compositions, disposablely obtain wrapping the medicine microsphere, concrete grammar is as follows:
Get a certain amount of non-promise fragrant calcium that falls and be dissolved in the glacial acetic acid, 5% chitosan solution and 10% fibroin solution compare blend by 1: 4 to 4: 1 quality.Blended liquid stirs and adds liquid paraffin 20～50mL after 30 minutes, sorbitan fatty acid ester 0.8～1.5g stirs after 20～40 minutes and adds ethyl acetate 2mL, fully stirring makes reaction system be emulsion, and keep and reacted 30 minutes, adding glutaraldehyde 1～2mL then stirred 1～2 hour, with acetone thorough washing solid product, product must wrap the medicine microsphere in 45 ℃ of following vacuum dryings.
Compared with prior art, adopt the obtained beneficial effect of technical measures of the present invention:
Technical scheme of the present invention has obvious improvement and innovation than existing technology: the present invention adds fibroin in chitosan, but and with the microsphere of formation rule behind the glutaraldehyde cross-linking bag medicine, and cavity arranged, and, fibroin also is the material to the PH sensitivity, can be under different PH conditions sustained release.These two kinds of compositions all are biodegradable materials in the body simultaneously, are the ideal materials as pharmaceutical carrier, and therefore, the present invention has important use at field of medicaments and is worth.
Below in conjunction with specific embodiment technical scheme of the present invention is further described:
Embodiment 1
The preparation of chitosan and fibroin mixed microsphere, chitosan are dissolved in the chitosan solution that gets 2% (w/w) in the acetic acid; The chitosan solution of (w/w) fibroin solution and 2% (w/w) with 1% is at normal temperatures in 1: 4 ratio blend of mass ratio, get above-mentioned blended liquid 10mL and liquid paraffin 20mL, anhydrous sorbitol laurate (Span-20) 0.8g adds ethyl acetate 2mL after mixing stirring 30min, glutaraldehyde 1.5mL uses acetone thorough washing solid product after stirring 2h, and product gets chitosan-heart protein mixed microsphere in 60 ℃ of following vacuum dryings.
Embodiment 2
The chitosan solution of (w/w) fibroin solution and 2% (w/w) with 1% is at normal temperatures in 4: 1 ratio blend of mass ratio, get above-mentioned blended liquid 10mL and liquid paraffin 30mL, Span-201.2g adds ethyl acetate 2mL after mixing stirring 30min, glutaraldehyde 1.5mL uses acetone thorough washing solid product after stirring 2h, and product gets chitosan-heart protein mixed microsphere in 60 ℃ of following vacuum dryings.
Embodiment 3
The chitosan solution of (w/w) fibroin solution and 2% (w/w) with 1% is at normal temperatures in 1: 1 ratio blend of mass ratio, get above-mentioned blended liquid 10mL and liquid paraffin 50mL, Span-20 1.0g adds ethyl acetate 2mL after mixing stirring 30min, glutaraldehyde 1.5mL uses acetone thorough washing solid product after stirring 2h, and product gets chitosan-heart protein mixed microsphere in 60 ℃ of following vacuum dryings.
The preparation of embodiment 4 bag medicine microspheres
Get 0.1g Fei Nuofen calcium and be dissolved in the glacial acetic acid of 5mL, get the fibroin solution blend of 20g 5% (w/w) chitosan solution and 20g 10% (w/w).Blended liquid adds liquid paraffin 40mL, Span-20 1g after stirring 30min, ethyl acetate 2mL, and fully stirring makes reaction system be emulsion, and keeps reaction 30min, adds glutaraldehyde 1.2mL then and stirs 2h.With acetone thorough washing solid product, product must wrap the medicine microsphere in 45 ℃ of following vacuum dryings.
Claims (4)
1, a kind of chitosan and fibroin mixed microsphere, it is characterized in that: this mixed microsphere is prepared by following method: fibroin solution with 1% and 2% chitosan solution are 1: 4 to 4: 1 ratio blend at normal temperatures in mass ratio, get above-mentioned blended liquid 10mL and liquid paraffin 10～50mL, hang acid esters 0.8～1.4g mixing stirring the anhydrous sorbitol moon and add ethyl acetate 2mL after 20～40 minutes, glutaraldehyde 1～2mL stirs and uses acetone thorough washing solid product after 1～2 hour, and product gets the chitosan fibroin mixed microsphere in 60 ℃ of following vacuum dryings.
2, described chitosan of claim 1 and fibroin mixed microsphere are as the sustained-release micro-spheres carrier of medicine.
3, a kind of method for preparing described chitosan of claim 1 and fibroin mixed microsphere, it is characterized in that: fibroin solution with 1% and 2% chitosan solution are 1: 4 to 4: 1 ratio blend at normal temperatures in mass ratio, get above-mentioned blended liquid 10mL and liquid paraffin 10～50mL, anhydrous sorbitol laurate 0.8～1.4g mixes stirring and adds ethyl acetate 2mL after 20～40 minutes, glutaraldehyde 1～2mL stirs and uses acetone thorough washing solid product after 1～2 hour, and product gets the chitosan fibroin mixed microsphere in 60 ℃ of following vacuum dryings.
4, a kind of fall method of fragrant calcium medicine microspheres of chitosan and the non-promise of fibroin mixed enclose medicine for preparing, it is characterized in that: get the quantitative non-promise fragrant calcium that falls and be dissolved in the glacial acetic acid, 5% chitosan solution and 10% fibroin solution compare blend by 1: 4 to 4: 1 quality, blended liquid stirs and adds liquid paraffin 20～50mL after 30 minutes, sorbitan fatty acid ester 0.8～1.5g stirs after 20～40 minutes and adds ethyl acetate 2mL, fully stirring makes reaction system be emulsion, and keep and reacted 30 minutes, adding glutaraldehyde 1～2mL then stirred 1～2 hour, with acetone thorough washing solid product, must wrap the medicine microsphere in 45 ℃ of following vacuum dryings.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB991200276A CN1235571C (en) | 1999-11-02 | 1999-11-02 | Chitosan and fibroin mixed microsphere and its usage and preparing process |
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| CNB991200276A CN1235571C (en) | 1999-11-02 | 1999-11-02 | Chitosan and fibroin mixed microsphere and its usage and preparing process |
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| CN1293952A CN1293952A (en) | 2001-05-09 |
| CN1235571C true CN1235571C (en) | 2006-01-11 |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003035124A2 (en) * | 2001-10-25 | 2003-05-01 | University Of Connecticut | Fibroin compositions and methods of making the same |
| CN101565515B (en) * | 2008-04-25 | 2011-05-11 | 西北师范大学 | Karaya gum complex polysaccharide microsphere used as bioactive molecular vector and preparation method thereof |
| CN102010601B (en) * | 2009-08-11 | 2012-11-21 | 南方医科大学珠江医院 | Macroporous micro-carrier with liver cell specificity as well as preparation method and applications thereof |
| US20120190113A1 (en) * | 2009-08-11 | 2012-07-26 | Yi Gao | Macroporous Microcarrier Specific to Liver Cell, Preparation Method and Use Thereof |
| CN101624473B (en) * | 2009-08-11 | 2012-10-10 | 南方医科大学珠江医院 | Method for culturing hepatic cells on a large scale |
| CN104928741B (en) * | 2015-05-21 | 2017-07-11 | 武汉大学 | How sensitive chitosan gel rubber of brick mud structure and its preparation method and application |
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1999
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